Population genetic analyses of Plasmodium falciparum chloroquine receptor transporter gene haplotypes reveal the evolutionary history of chloroquine-resistant malaria in India

• Published in: International journal for parasitology 2011-06, Vol.41 (7), p.705-709
• Main Authors: Awasthi, Gauri, Prasad, G.B.K.S., Das, Aparup
• Format: Article
• Language: English
• Subjects: Animals; Antimalarials - pharmacology; Biological and medical sciences; Chloroquine - pharmacology; Chloroquine resistance; DNA, Protozoan - chemistry; DNA, Protozoan - genetics; Drug Resistance; Evolution, Molecular; Fundamental and applied biological sciences. Psychology; Genetics of eukaryotes. Biological and molecular evolution; Haplotypes; Human protozoal diseases; Humans; India; India - epidemiology; Infectious diseases; Life cycle. Host-agent relationship. Pathogenesis; Malaria; Malaria, Falciparum - epidemiology; Malaria, Falciparum - parasitology; Medical sciences; Membrane Transport Proteins - genetics; Molecular Sequence Data; Parasitic diseases; Pfcrt haplotypes; Plasmodium falciparum; Plasmodium falciparum - drug effects; Plasmodium falciparum - genetics; Plasmodium falciparum - isolation & purification; Population genetics, reproduction patterns; Protozoa; Protozoal diseases; Protozoan Proteins - genetics; Sequence Analysis, DNA
• ISSN: 0020-7519; 1879-0135
• DOI: 10.1016/j.ijpara.2011.03.002

[Display omitted] ► DNA sequence data analyses provide information on the evolutionary history of genes and species. ► Pfcrt gene data were utilized to infer evolutionary history of chloroquine resistance in India. ► Utilizing this approach, high prevalence of the SVMNT haplotype in India has been explained. ► Detailed migration route of SVMNT and CVIET haplotypes to India was inferred. ► The approach can be applied in monitoring resistance patterns in other infectious diseases. Inferring the origin and dispersal of the chloroquine-resistant (CQR) malaria parasite, Plasmodium falciparum, is of academic and public health importance. The Pfcrt gene of P. falciparum is widely known as the CQR gene and two major haplotypes of this gene (CVIET and SVMNT) occur widely across CQR-endemic regions of the globe. In India, studies to date of the Pfcrt gene have indicated the widespread prevalence of the SVMNT haplotype (prevalent in the South America and Papua New Guinea), whereas the CVIET haplotype, primarily found in southeast Asia, was not detected at a high frequency in India. This distribution pattern of the two most common CQR- Pfcrt haplotypes in India is quite surprising. Thus, in order to understand probable evolutionary and migration patterns of the CQR- Pfcrt haplotypes into India, we generated new sequence data of exon 2 of the Pfcrt gene and collected published information on the CQR- Pfcrt haplotype data from India, Papua New Guinea, southeast Asia and South America, and performed several population and evolutionary genetic analyses. Among several interesting findings, statistically significant longitudinal clines for the CVIET and SVMNT haplotypes (in opposite directions) in India, and the clustering of India and Papua New Guinea under the SVMNT-specific clade in the phylogenetic tree, are the two most remarkable aspects of the data. It also appears that both the SVMNT and CVIET haplotypes in India have migrated from southeast Asia. In particular, whereas the Indian CVIET haplotype has a southeast Asian origin, the SVMNT haplotype, prevalent in India, seems to have originated in Papua New Guinea and entered India through southeast Asia.